The nuclear import factor importin alpha 4 can protect against oxidative stress

Young, Julia C., Ly-Huynh, Jennifer D., Lescesen, Helen, Miyamoto, Yoichi, Browne, Cate, Yoneda, Yoshihiro, Koopman, Peter, Loveland, Kate L. and Jans, David A. (2013) The nuclear import factor importin alpha 4 can protect against oxidative stress. Biochimica et Biophysica Acta (BBA): Molecular Cell Research, 1833 10: 2348-2356. doi:10.1016/j.bbamcr.2013.06.007


Author Young, Julia C.
Ly-Huynh, Jennifer D.
Lescesen, Helen
Miyamoto, Yoichi
Browne, Cate
Yoneda, Yoshihiro
Koopman, Peter
Loveland, Kate L.
Jans, David A.
Title The nuclear import factor importin alpha 4 can protect against oxidative stress
Formatted title
The nuclear import factor importin α4 can protect against oxidative stress
Journal name Biochimica et Biophysica Acta (BBA): Molecular Cell Research   Check publisher's open access policy
ISSN 0167-4889
Publication date 2013-10
Sub-type Article (original research)
DOI 10.1016/j.bbamcr.2013.06.007
Open Access Status
Volume 1833
Issue 10
Start page 2348
End page 2356
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2014
Language eng
Formatted abstract
Highlights
• Two novel in vivo models developed to investigate IMPα4 function in male germ cells
• Increased IMPα4 levels do not disrupt spermatogenic progression or fertility.
• Increased IMPα4 levels confer protection against oxidative stress-induced cell death.
• Absence of IMPα4 leads to increased sensitivity to oxidative stress.
• Data implicate IMPα4-mediated stress responses in supporting male fertility.

The importin (IMP) superfamily of nuclear transport proteins is essential to key developmental pathways, including in the murine testis where expression of the 6 distinct IMPα proteins is highly dynamic. Present predominantly from the spermatocyte stage onwards, IMPα4 is unique in showing a striking nuclear localization, a property we previously found to be linked to maintenance of pluripotency in embryonic stem cells and to the cellular stress response in cultured cells. Here we examine the role of IMPα4 in vivo for the first time using a novel transgenic mouse model in which we overexpress an IMPα4–EGFP fusion protein from the protamine 1 promoter to recapitulate endogenous testicular germ cell IMPα4 expression in spermatids. IMPα4 overexpression did not affect overall fertility, testis morphology/weight or spermatogenic progression under normal conditions, but conferred significantly (> 30%) increased resistance to oxidative stress specifically in the spermatid subpopulation expressing the transgene. Consistent with a cell-specific role for IMPα4 in protecting against oxidative stress, haploid germ cells from IMPα4 null mice were significantly (c. 30%) less resistant to oxidative stress than wild type controls. These results from two unique and complementary mouse models demonstrate a novel protective role for IMPα4 in stress responses specifically within haploid male germline cells, with implications for male fertility and genetic integrity.
Keyword Spermatogenesis
Oxidative stress
Nuclear transport
Importin/karyopherin
Regulated nucleocytoplasmic transport
Germ-cell maturation
Male-infertility
Spermatogenesis
Expression
Differentiation
Localization
Subunits
Beta
Line
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 08 Sep 2013, 00:10:43 EST by System User on behalf of Institute for Molecular Bioscience